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Biomedical subjects

A Mazzoni

Publications and source records attributed to A Mazzoni.

At least 91 records · Page 5Linked to original sources

Generation and characterization of a low-degree drug-resistant human tumor cell line.

A 2780 human ovarian cancer cells, obtained from an untreated patient, have been exposed to a relatively low, clinically maintainable dose (10 nmol/l) of the anthracycline doxorubicin (DX) to derive a low-degree (5-fold) drug-resistant subline (A2780-DX1). Compared to parental cells, these DX-resistant cells have increased size (+60% of cell volume) and contain a greater number of cytoplasmic vacuoles as determined by electron microscopy. When exposed to several other antiproliferative drugs, A2780-DX1 cells were highly cross-resistant (greater than 10-fold) to epirubicin, mafosfamide and cisplatin and slightly cross-resistant (2- to 3-fold) to navelbine and bleomycin, while they retained the original sensitivity to vinblastine, Ara-C and fluorouracil. Gel electrophoresis of cytoplasmic membrane proteins showed differences between the pattern of parental A2780 sensitive and A2780-DX1 cells as far as low-molecular-weight proteins (less than 45 kD) are concerned, while no clear overexpression of P-glycoprotein (P-170) could be detected. Membrane modifications yielding a decrease of both DX uptake and retention, increased content of intracellular glutathione (+32%) and reduced DNA double-strand breaks seem to be involved in the resulting multidrug-resistant phenotype of A2780-DX1 cells.

Antineoplastic Agents↗

The vascular anatomy of the vestibular labyrinth in man.

1. A survey of the literature on the vascular anatomy of the vestibular labyrinth in Man is presented, and the methods of investigation used to visualize the vessels are evaluated. A generally correct picture of the subject is provided by the various studies published since Siebenmann's monograph. There are, however, some conflicting points as well as some lack of data with regard to the course and relationships of the large vessels and the capillary areas of the cristae and maculae. 2. This study presents a systematic description of the vascular anatomy of the vestibular labyrinth in Man, from the main arterial and venous stems to the capillary areas, with particular attention to the relationships between the vessels and the osseous walls, neural, and membranous structures. The vessels were visualized by a composite method including the selective injection of the internal auditory artery with coloured silicone or India ink; the counterstaining of the labyrinth with osmic acid; the cutting of the petrous bone in 1-mm thick, serial sections that were cleared with methylsalicylate. The sections were studied by stereomicroscopy, using mainly reflected light. Photos and drawings were made to illustrate the findings. New names were introduced for vessels hitherto unnamed, and some traditional names were modified in order to give a more precise and descriptive terminology. 3. The description followed the two main arteries, the capillary areas and the three main veins. The vestibular labyrinth is supplied by the superior vestibular artery and by the inferior vestibular artery which is a branch of the vestibulo-cochlear artery. The superior vestibular artery runs along the anterior aspect of the vestibule from the utricular nerve up to the cristae of the superior and lateral canals. It supplies the macula of the utricle, the cristae and ampullar crures of the superior and lateral canals. The inferior vestibular artery runs mainly along the medial wall of the vestibule. It supplies the last tract of the scala media and the vestibular caecum with a peculiar pattern which appears to be an adaptation of the common cochlear arrangement to the different spatial condition. It also supplies the macula of the saccule, the crista and ampullar crus of the posterior canal as well as the simple crures of the three canals. The vascular arrangement of the maculae and cristae has a similar three-layered architecture.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteries↗

Relationship between cytotoxicity, drug accumulation, DNA damage and repair of human ovarian cancer cells treated with doxorubicin: modulation by the tiapamil analog RO11-2933.

The effect of N-(3,4-dimethoxyphenyl) N-methyl-2-(naphthyl)-m-dithiane-2-propylamine hydrochloride (RO11-2933), an analog of the calcium channel blocker tiapamil, on doxorubicin (DOX)-induced cytotoxicity and DNA damage in human ovarian cancer cells sensitive and resistant to DOX was investigated. A2780-DX2, A2780-DX3, and A2780-DX6 cell sublines were characterized by 7-, 26-, and 48-fold resistance after 2 h DOX exposure and 30-, 50-, and 500-fold resistance after 72 h DOX exposure, respectively. Increased drug efflux resulting in a lower intracellular drug accumulation, decreased DOX-induced DNA single-strand breaks (DNA SSBs), and rapid DNA repair correlated with the degree of resistance. In addition, DNA SSBs were rapidly repaired within 8 h in A2780-DX3 cells, whereas no significant repair of DNA SSBs was observed in sensitive cells. In comparison with verapamil, RO11-2933 was found to reverse DOX resistance at lower and nontoxic concentrations (2 microM as compared with 10 microM verapamil). This reversion was complete in cells with a low degree of resistance (A2780-DX1 and A2780-DX2) but partial in highly resistant cells (A2780-DX3 and A2780-DX6), and continuous exposure to RO11-2933 was essential for optimal reversal of drug resistance. Interestingly, RO11-2933 was found to inhibit the repair of DNA SSBs induced by DOX but not those induced by X-ray. These results suggest that the potentiation of DNA SSBs and the specific inhibition of DNA repair by RO11-2933 in multidrug-resistant cells could be of particular value in overcoming MDR in the clinic.

Calcium Channel Blockers↗

Retrolabyrinthine versus middle fossa vestibular neurectomy.

The authors' experience in treating incapacitating peripheral vertigo using the middle cranial fossa (MCF) and the retrolabyrinthine (RL) approaches is presented. Among 94 operated cases, 56 have been treated using the MCF approach and 38 the RL approach. In 18 of the RL cases, a simple vestibular neurectomy has been associated with different adjunctive techniques (i.e., drainage of the endolymphatic sac, section of the Wrisberg intermediary nerve, and neurovascular decompression of the eight nerve) in an attempt to influence the disease from a pathogenetic viewpoint. The RL approach has demonstrated to be a valid alternative to the MCF approach, since it allows the same results to be obtained in the control of vertigo, with fewer risks to the facial nerve and hearing functions. Moreover, it allows the association, although still in an experimental way, of the simple vestibular neurectomy and the other "pathogenetic" methods mentioned above.

Adult↗

Intratemporal vascular tumours.

Hemangiomas of the temporal bone are uncommon benign tumours, occurring most frequently at two sites: the internal auditory meatus (IAM) and the geniculate ganglion. In this paper the authors discuss the pathology, clinical onset and features, and the therapeutic management of two of these lesions. A review of the literature is also presented, paying attention to the controversy regarding the origin, pathogenesis and histologic classification of this rare lesion of the temporal bone.

Adult↗

Incidence of endogenous and exogenous opportunistic fungal infections in relation to different prophylactic measures: clinical and microbiological study of 431 immunocompromised patients.

Two groups of immunocompromised patients were studied with the aim of pointing out the possibilities of antifungal prophylaxis in this type of patient. All patients received oral treatment with nystatin, but only the patients of one group were also in strict reverse isolation. It has been confirmed that chemoprophylactic treatments may control opportunistic endogenous mycoses effectually. On the contrary, only reverse isolation seems to be effective against airborne exogenous fungal infections. Because of the difficulty and high cost of this practice, different modalities for a really generalizable antifungal prophylaxis are required. At present only the detection of new systemic antifungal drugs, which are not toxic and are easy to use, seems hopeful.

Fungi↗

Hearing preservation in acoustic neuroma surgery. Middle fossa versus suboccipital approach.

Over the past few years there have been reports discussing the preservation of hearing after the removal of acoustic neuromas through the middle cranial fossa or the suboccipital approaches. This is a complex issue with many facets and controversies. In an attempt to answer at least some of these controversies, this article reviews the experience of our group. Preservation of hearing was attempted in thirty-four cases out of 220 acoustic neuromas. In twenty cases the middle fossa approach was used: All tumors were less than 2 cm from the fundus, and in four patients the tumor was bilateral. In sixteen of the twenty (80%) the cochlear nerve was spared; in ten of twenty (50%) measurable hearing was retained, but in only four (20%) was the postoperative hearing serviceable according to the 50/50 rule. In fourteen cases the suboccipital approach was used: All but two of the tumors were smaller than 2 cm. In three patients the tumor was bilateral. The cochlear nerve was preserved in ten of the fourteen cases (71.4%). Measurable hearing was present in four of fourteen cases postoperatively (28.6%); none had serviceable hearing according to the 50/50 rule. Hearing was not preserved in any bilateral tumor case. The middle fossa and the suboccipital approaches are discussed as well as the relative merits of each procedure in preservation of hearing.

Adult↗

Comparative distribution of free doxorubicin and poly-L-aspartic acid linked doxorubicin in MS-2 sarcoma bearing mice.

The plasma and tissue distribution of doxorubicin-poly-L-aspartic acid (DX-PAA) and doxorubicin (DX) at equitoxic doses have been studied by a fluorescence assay in tumor bearing mice following administration of a single i.v. bolus injection. A relatively short distribution phase followed by a slow elimination phase characterized the DX-PAA plasma disappearence: at 48 hr after the treatment the conjugate was still detected in plasma. The plasma under the concentration vs. time curve (AUC) of drug equivalents following free DX administration resulted 2.6 times higher than the plasma AUC of free equivalents produced by DX-PAA treatment. In lung, liver and spleen the DX-PAA was accumulated in high concentrations. Low amount of DX equivalents were found in the heart following the conjugate administration: after 2 hr only traces of free anthracycline equivalents were detectable. On the contrary, drug equivalents following free DX treatment remained evaluable in the heart up to 24 hr from the drug administration. No significative differences were observed in the tumor AUC of free DX equivalents produced by free or polymer-linked DX. These data suggest that DX-PAA might act as a depot system slowly releasing the cytotoxic agent. Furthermore the observed accumulation of the conjugate and free DX equivalents in the lung and in the liver suggest a possible therapeutic advantages of DX-PAA in tumors with potential metastasis in these organs.

Animals↗

Microsurgery in nasal polyposis transnasal ethmoidectomy.

Transnasal ethmoidectomy is a current treatment in selected cases of nasal polyposis, and with its complicated anatomy offers a proper opportunity for microsurgery. Ten years' experience of microsurgical ethmoidectomy in 155 patients with nasal polyposis is reported. The surgical anatomy of the ethmoid sinus is reviewed with attention to the requirements of the microsurgical approach, and the operative procedure is described. The microsurgical approach is discussed both as a part of the treatment of nasal polyposis and as a new development in rhinologic surgery. Advantages of the technique are the objective safety against risks of the ethmoid area and enhanced sense of security for the surgeon.

Adult↗